S13
Oxygen Transport and Cardiovascular Function at Extreme Altitude: Lessons from Operation Operafion Everest II John R. Sutton1, John T ron M. Peter D.Wagner3, Wagner3, James James K. K. Alexander4, Alexander4, T.Reeves2, Reeves2,Bert Bertron M Groves2, PeterD. Cymerman6 and Charles S. Houston7 AllenCyrnerman6 and Charles S. Houston7 Herbert N. Hultgren5 , Allen 'Department of Biological Sciences, Faculty of Health Sciences, The University of Sydney 2Department of Medicine, University of Colorado, Denver, CO, U. S. A. 3Department of Medicine, University of California, San Diego, La Jolla, CA, U. S. A. 92093 4Department of Internal Medicine, Baylor College of Medicine, Houston, TX, U. S. A. 77030 5Department of Cardiology, Veterans' Administration Medical Centre, Palo Alto, CA, U. S. A. 94304 6Altitude Research Division, U. S. Army Research Institute of Environmental Medicine, Natick, MA, U. S. A. 01760-5007 7Department of Medicine, Vermont, Burlington, VT, U. S. A. Medicine, University University of ofVermont, A. 04501 04501
Abstract John R. Sutton, John T. Reeves, Bertron M. Groves, Peter D. Wagner, James K. Alexander, Herbert N. Hultgren, Allen Cymerman and Charles S. Houston, Oxygen
Transport and Cardiovascular Function at Extreme Altitude: Lessons from Operation Everest II. Tnt J Sports Med, Vol 13,Suppl 1,ppSl3—518, 1,ppSl3—Sl8, 1992.
Operation Everest II was designed to examine the physiological responses to gradual decompression simulating an ascent of Mt Everest (8,848 m) to an inspired P02 of 43 mmHg. The principal studies conducted were cardiovascular, respiratory, muscular-skeletal and metabolic responses to exercise. Eight healthy males aged
21—31 years began the "ascent" and six successfully reached the "summit", where their resting arterial blood mmHg and andPCO2 PCO2 11 11mmHg, mmHg, pH pH gasses were P02 = 30 mmHg = 7.56. Their maximal oxygen uptake decreased from L/minatatsea sealevel level to to 1.17 1.17 0.08 0.08 L/min at P102 3.98 0.2 L/min 3.98 43 mmHg. The principal factors responsible for oxygen transport from the atmosphere to tissues were (1) Alveolar ventilation — a four fold increase. (2) Diffusion from the alveolus to end capillary blood — unchanged. (3) Cardiac function (assessed by hemodynamics, echocardiography normal — although although maximum and electrocardiography) — normal cardiac output and heart rate were reduced. (4) Oxygen extraction — maximal with Pv02 14.8 1 mmHg. With in-
creasing altitude maximal blood and muscle lactate progressively declined although at any submaximal intensity blood and muscle lactate was higher at higher altitudes. Key_words
Altitude, exercise, cardiac output, hypobaric chamber, chamber, pulmonary pulmonary circulation circulation
mt. J.J.Sports Tnt. SportsMed. Med.13(1992)S13 l3(l992)S13 — S18
GeorgThieme Georg ThiemeVerlag VerlagStuttgart StuttgartNew New York
In the world of mountain medicine, there are four dates in this century of particular significance. At these times, important knowledge was gained about adaptations to extreme altitude on Mount Everest. On the first, May 29, 1953, Edmund Hillary and Tenzing Norgay reached the summit. Electrocardiograms of four climbers were telemetered from the summit in May of 1975 during the Chinese Mount Qomolangma expedition (12). On May 8, 1978, Peter Habeler and Reinhold Messner completed the first ascent of of Mount Mount Everest Everest without the use of supplementary oxygen. oxygen. On On October October
24, 1981, Chris Pizzo made the first measurements of barometric pressure and other physiological variables on the summit (16). On each occasion, significant new knowledge was was gained gained which which helped helped our our understanding understanding of of altitude altitude physiphysiology. The first piece of information was that the summit of Mount Everest could be reached by humans. The second was that some measurements could be made. The third was that it was not necessary to use supplementary oxygen to accomplish the climb. However, as was clear from the American Medical Research Expedition to Everest which made some simple, non-invasive measurements, and from experience in other mountain locations, detailed physiological measurements at extreme altitudes, particularly those involving invasive techniques, were highly risky, if not impossible, at our present state of knowledge and technology.
Two other dates are important in the world of mountain medicine. They are July 30, 1946 and November 8, 1985. On the first date, two subjects reached a barometric pressure of 235 Torr in a small hypobaric chamber during the historic Operation Everest study conducted by Charles Houston and Dick Riley (5). In the second instance, six subjects were taken to a barometric pressure pressure of of 234 234 Torr Torr during during the the study study
Operation Everest II under the the investigative investigative guidance guidance of of Charles Houston, Allen Cymerman and John Sutton (6). Although both Operation Everest and its successor, Operation Everest II (OEII), were prolonged hypobaric chamber studies and nearly 40 years elapsed between the studies, perhaps the most remarkable fact was that Charles Houston was a principal investigator of both projects.
The principal objectives of OEII were to examine all the physiological variables which determine oxygen
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Introduction
514 mt. S14 mt. .1. i Sports SportsMed. Med.13(1992) 13(1992)
I R. J. R.Sutton, Sutton,IITTReeves, Reeves, B. B. M M Groves, Groves, P. P. B. B. Wagner, Wagner, I K. Alexander etal.
transport, from the lung and alveolar ventilation to oxygen extraction at the tissue level, and muscle structure and function (4,6, (4, 6,10, 10, 14, 14, 15). 15). In In order order to to do do this, this, a variety of exercise studies were performed including the measurement of maximal oxy(VO2max)(l). gen uptake (VO2max) (1).Invasive Invasivestudies studieswere weremade madein inwhich which
an arterial line and a Swan-Ganz catheter were inserted to measure pulmonary hemodynamics, arterial blood gases and cardiac output directly using the Fick technique. In addition, a
ASCENT PROFILE F 02 F 02 Torr Torr 43 49
63 80
superficial venous line was inserted for the infusion of inert gases to quantify ventilation/perfusion relationships (15). In a third study, venous blood and muscle biopsy samples were taken after exercise to exhaustion (3, 14). Two additional exercise studies were performed to gain further information on car-
/ 150
L5
10 15
20 25 30 35 40
DAYS AT ALTITUDE
diac function. One was two-dimensional echocardiography (13) and the other was 12-lead electrocardiograms (8). Fig.
1 Ascent profile of Operation Everst II.
ergometer, a treadmill, a table, a water fountain and chairs.
ter Calibration Curve is lower than either of these, projecting a figure of approximately 235 Torr for the summit. This figure has has been been used used traditionally traditionally in in all all decompression decompression chamber chamber stustudies since, including Houston and Riley's original Operation Everest project. However, when measurements were made at extreme altitudes in the Himalaya by Pugh in 1957 (9) and Gill and coworkers in 1962 (2), the derived figure for the summit of Mt. Everest was 250 Torr. In 1981, on the AMREE trip, Pizzo
The smaller room was the principal study site. In the lock were
recorded a measurement of 253 Torr, confirming the earlier
placed a toilet and shower and the "Versaclimber" used to
work of Pugh and colleagues (9).
The decompression chamber consisted of two rooms, 6.1 x 2.7 m and 2.7 2.7 xx 3.7 3.7 m m in in size, size, connected connected by byan an airlock of 2.7 x 2.1 m which could be decompressed independently of the rooms. In each chamber, there was a small pass-through lock to enable the shipping out of samples and the shipping in of food. The larger room served as the living
quarters and contained four double bunk beds, a cycle
enable the subjects to simulate climbing.
Operation Everest II Subjects The The subjects were all men, ranging in age from 21 to 31 years, of varying backgrounds from bicycle mechanic and draftsman to medical students and physicians.
After extensive studies at sea level, the chamber ber doors were closed and for 40 days and nights, nights, the the subjects subjects were were gradually gradually decompressed decompressed (Fig. (Fig. 1). 1). On On three three occasions, occasions, at at barometric pressures of 429, 380 and 347 Torr, the chamber was kept constant for several days to enable the scientists to perform more detailed and invasive studies of all the subjects at one pressure. When the chamber was decompressed to 308 Torr, the equivalent of 7,010 m, the subjects had difficulty sleeping, so the chamber pressure was reduced each night by 4—6 Torr to effectively accomplish what mountain climbers do — climb high and sleep low. Finally, on day 34, November 8,
1985, we had our first "summit run", taking the subject from 282 Torr to a final barometric pressure of 234 Torr, over 9,000 m, without any ill effects. This demonstrated to the subjects that they were capable of reaching this simulated altitude and was very important psychologically since they knew that the next time they were to reach the summit, they would be required to perform a maximal exercise test with indwelling arterial and central venous lines. Over the course of the next week, the subjects were studied at 282 Torr and gradually decompressed to the equivalent of the summit of Everest.
Paul Bert suggested that the barometric pressure on the summit of Mt. Everest would be approximately 250 Torr. Earlier in this century, Zuntz and colleagues made measurements as high as 4,980 m and predicted a much higher pressure for that summit — 269 Torr (17). The International Altime-
In the autumn of 1985, a group of 26 scientists and 8 subjects embarked on the Operation Everest II project.
The main purpose was to examine in detail components of oxygen transport during exercise at extreme simulated altitude. Although detailed measurements were made of psychology, body composition, nutritional status, muscle biochemistry, structure and function, endocrine function and control of breathing at rest and during sleep, in this paper we shall detail the features of oxygen transport and emphasize cardiac function.
Several exercise studies were were performed performed in in order to quantify oxygen transport and cardiovascular function. They include: I. An 1. An interrupted interrupted VO2max test to quantify maximal oxygen uptake — also also at extreme altitude 12-lead electrocardiographs were taken looking for morphological changes related to pulmonary hypertension and also seeking evidence of of myocardial ischemia. 2. 2. A progressive exercise test to exhaustion, with with the the workload workload beginning at 30 W and increasing in 30 W increments each minute. This test was used to quantify maximum power output, maximum heart rate, exercise symptoms of leg fatigue and dyspnea, and maximal blood lactate. At rest and exhaustion in this test, muscle biopsy samples were taken from the vastus lateralis for analysis of enzymes, muscle metabolites and muscle ultrastructure. 3. Two-dimensional echocardiograms with pulsed Doppler recordings were performed at rest and during exercise at various altitudes from sea level up to and including the equivalent of the summit of Mt. Everest.
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The Chamber
Jnt.J.J. Sports mt. Sports Med. Med. 13 13(1992) (1992) S15
Oxygen Transport and Cardiovascular Function at Extreme Altitude
4. Several levels of steady-state exercise up to and in some cases including maximal oxygen uptake with indwelling brachial or radial arterial lines and a Swan-Ganz flowdirected thermodilution catheter inserted into the pulmonary artery. In addition, a superficial venous catheter was
weighing and computerized axial tomography scans con-
inserted to enable us to infuse various inert gases to quantify
sea level level value, value,from fromaamean meanofof5050ml-kg-min mlkgmin'at the sea 'at sea sea level kg level to to15 15mlml-kgmin' on"thesummit"(Fig.2). on "the summit" (Fig. 2).
ventilation/perfusion relationships. This study included
firmed that both fat and lean muscle tissue were lost during the course of this decompression (11).
Maximal oxygen uptake decreased by 72% of
the most invasive procedures and gave us the opportunity to
of the direct Fick technique to quantify cardiac output. Findings and Implications of Operation Everest II
Of the eight subjects who began the study, two were removed from the chamber prematurely for hypoxic episodes, but six were able to reach the "summit" and exercise. Over the course of 40 days and nights, there was a mean weight loss of 7.44 kg (8.9%) as the subjects had a marked reduction (42%) in caloric intake despite being provided with excellent
and appetizing meals. Skinfold measurements, underwater
60 MeanSEM
50 C
There were progressive changes changes in in the the resting resting electrocardiograms: an increase increase in in P-wave P-wave amplitude, amplitude, aaright right axis shift in the frontal plane — compatible compatible with pulmonary hypertension with increasing altitude. No arrythmias, conduction defects, ST- or T-wave changes to suggest ischemia were observed despite profound hypoxemia (8). In the progressive exercise test to exhaustion, with increasing altitude, exercise performance was decreased,
accompanied by a diminished maximum heart rate and increased ventilation. At extreme extreme altitude, altitude, the the overwhelming overwhelming symptoms of dyspnea and leg fatigue were of a comparable order of magnitude, each reaching 9.5 on the Borg 0—10 scale.
In this study, blood lactate was also analyzed and at exhaustion, showed a progressive decrease from 12.7 mmol-F 1at theequivalent equivalent of of the summit of of sea level level to to 3.4 3.4mmol-F mmolF 1atatthe Mt. Everest (14). The muscle biopsy samples taken at exhaustion showed a progressive decrease in muscle lactate at exhaustion with increasing altitude (3).
In the echocardiographic study, all subjects 40 40
had a decreased left ventricular end-diastolic and end-systolic
30
volume and stroke volume decreased progressively. progressively. These These changes were of these orders of magnitude: 21%, 40% and
a,
14% respectively at a barometric pressure of 282 Torr (Fig. 3). There were comparable decreases during exercise at 60 W intensity. 1n addition, indices of left ventricular systolic function — ejection fraction, the ratio of peak systolic pressure to endsystolic volume, and the mean normalized systolic ejection rate — were were either maintained or slightly enhanced at altitude, suggesting a modest increase in left ventricular contractility at altitude (13; Fig. 4). During maximal exercise, no ST-T wave
•: 0-
______________
I—I I
434963
I 150
I
80
changes were seen in the electrocardiogram to suggest
P102 Torr
ischemia or left ventricular dysfunction and no significant arrhythmias occurred.
Fig. Fig. 2 VO2max 'O2max with with altitude. altitude.
Fig. Ejection fractions fractions at at rest rest on on the the Fig. 33Ejection
an —
80
80
70
70
60
60
50
50
EjectIon Ejection Fraction FracUon
(°/)
cycle ergometer and during peak exercise in all sublects subjects studied at sea level and at a barometric pressure of 282 Torr. (Reprinted with permission from reference 12.)
Mean
Mean
40L Cycle
Peak
Cycle
Rest
Exercise
Rest
Sea Levet Level
Peak Exercise
8 282 torr
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measure arterial and mixed venous blood gases and systemic and pulmonary hemodynamics, together with the use
I R.R.Sutton, .1. Sutton, II T Reeves, Reeves, B.B.MMGroves, Groves, P. D. P. Wagner, D. Wagner, J. K. J. Alexander K. Alexander ci al. el al.
S16 mt. I Sports Med. 13(1992) 12
Ô L/min
P 282 torr 10 O—O P9 380 torr
b— Sea Level Ratio Peak Systolic Pressure: End-Systolic Volume Vol urn e (rnrn Hg/rnI) (mm Hg/mi)
24 20
8 6
.150 £80
16 12
4
2 I
CI C
Peak Exercise
Cycle Rest
(Torr) •63 V 49 .43
8 4 0
POWER OUTPUT WATTS
Fig. 4 Mean ratios of peak systolic pressure to end-systolic volume volume at at rest rest on on the the cycle cycle ergometer ergometer and and during during peak peak exercise exercise for for a!! subjects studied at sea eveJ, all level, and barometric barometric pressures pressures of of 380 380 Torr and 282 Torr. (Reprinted with permission from reference 12).
60 120 180 240 300 360
Fig. 5 Cardiac output during exercise with increasing simulated
There There were substantial changes in the right side of the heart. As noted earlier, there was a rightward of rightward deviation deviation of the mean QRS axis in the frontal plane on the electrocardiogram; this was presumably a concomitant of the pulmonary hypertension. There was also a moderate right ventricular enlargement and paradoxial septal wall motion seen on the echocardiogram (13). Right ventricular filling pressures (denoted by right atrial mean pressure) did not increase with altitude, nor did the Doppler examination reveal evidence of tricuspid valve valve incompetence. incompetence. Left Left ventricular ventricular filling tilling pressure also remained normal or decreased with increasing altitude altitude expoexposure, as reflected by pulmonary artery wedge pressure. This may be related, in part, to a decrease in plasma volume. We concluded from the echocardiographic studies that ventricular function remained normal, was even enhanced and was not a limiting factor in exercise performance at extreme altitude.
The most comprehensive exercise studies performed in OEII enabled us to quantify all aspects of oxygen transportation as we had indwelling arterial and pulmonary artery catheters. Our principal observations indicated that the major adjustments in the oxygen transport system which allowed exercise to be performed at extreme altitude were adaptations in ventilation, an increase in hemoglobin and in maximizing oxygen extraction (14). The chief value of arterial and mixed venous blood gases at VO2max are seen in Table 1. On
"the summit", P02 fell to 27.6 Torr at 120 W exercise. The lowest individual oxygen tension was 26 Torr, with with aa mean mean oxygen uptake of 1.18 l-min1. 1min1. The inert gas studies of of WagWagner ner and colleagues (15) showed that with increasing increasing altitudes altitudes below 429 Torr, the widening of the alveolar to arterial oxygen tension difference ((A — a)D02) became increasingly due to to aa
diffusion limitation and less due to the ventilation-perfusion mismatch.
Cardiovascular physiology in this study revealed vealed that that cardiac cardiac output output for for aa given given oxygen oxygen uptake uptake was was simisimi-
lar at all altitudes, although perhaps slightly higher on "the summit" (Fig. 5); however, the potential advantage of increas-
ing cardiac output to offset the marked arterial desaturation and decreased arterial oxygen content was not used. Resting pulmonary artery pressure and pulmonary vascular resistance increased from sea level to to maximum maximum values values at at PB PB 282 282 Torr Torr from 15 to to 34 34 mmHg mmHgand andfrom from1.2 1.2toto4.3 4.3mmHg-l-min1remmHglmin1respectively (Fig. 6). The increase was magnified during exercise, where the pulmonary artery pressure at sea level was 33 mmHg, rising to 54 mmHg at 282 Torr. Right atrial and pulmo-
nary artery wedge pressures did not increase at altitude, nor did systemic arterial pressure or systemic vascular resistance (Fig. 7). Conclusion
Table 1
VO2max, arteria' arterial (Pa02) (Pa02) and and mixed mixed venous venous(PV02) (PO2) oxygen oxygen tension at maximum exercise at different simulated altitudes. At the highest simulated altitude, a pressure of 240 Torr was required to give a Pi02 of 43 Torr as the inspired oxygen concentration had increased to 22% due to the excess oxygen exhaled by the scientists who were breathing 100% oxygen while working in the chamber. This is further detailed in reference 5. PB Pa (Torr)
P102 Pi02
n
760 429 347
150
282 240
49
80 63 63 43
8 8
7 5 5
Pa02
VO2max
(mImin (mImin
(Torr)
1)
(Torr)
PV02 PO2 (Torr)
3980 3,980 2,820 2060 2,060
87.3 87.3 41.9
18.5 ———
33.7
12.4
1770 1,770
33.1
14.1
1170 1,170
27.6
13.8
The Operation Everest II studies gave us some insight into how it is possible to climb to the equivalent of the summit of Mt. Everest without the use of supplementary oxygen. Performing exercise which can require more than one liter of oxygen but in which arterial oxygen tension is less than 30 Torr, the major mechanisms which come into play are: 1. a four-fold increase in ventilation 2. a 33% increase in hemoglobin 3. maximal oxygen extraction (Fig. 8)
Ventilation-perfusion studies indicated that gas transfer in the lung is primarily diffusion-limited. While ventilation/perfusion inequality inequality is is considerably considerably increased increased
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altitude.
:
mt. J. Sports Med.13 13(1992) Int.J.SportsMed. (1992) S17
Oxygen Transport and Cardiovascular Function at Extreme Altitude 50 50-Pulmonary 40 Vos culor Vascular Pressure 30 30 Gradient (PAM—PAWU)
20 -
(mml-4g) (mmkg)
0
C
a
• 0-
n—6
5/ .,
-
I
j
p/
•,L7' //P8 P6=240 =240
I
I
10 20 io 20
o 0
Fig. 6 Relationships of mean pulmonary
, •IS
/ ' a—2.77±.65 '0 b——1±bO b— —1±10 '0 n3
i:. •
I- 1I20 30
10
'
n—2
S7 / IS "S
b—12±2 b—12±2
a—24±.07 a—.24±.07
10 --
b—lU b-b
12 a— 1. 09± .12 01,09±.
P8 = 760 760 b—6±1 n—B n—B
B282 a—2.36 o—2.36 P8 = 282
P =347 PB=347
0
20
10
vascular pressure gradient [pulmonary arterial mean pressure (PAM) — pulmonary arterial wedge mean pressure (PAWM)] to thermodilution modilution cardiac output at various barometric pressurs (PB). Measurements are shown for PB 760, 347, 282 Torr (filled
circles) and 240 Torr (open circles). A regression line, y = ax + b , was calculated ca)culated for each subject at at each each PB. Pa. Shown, averaveraged for each PB, are slopes &opes (a) and intercepts (b) of regression equations, number of subjects (n), and regression line for group. (Reprinted with permission from reference 7).
Cardiac Output CL/mm)
Systemic
140 Vascular 140Vosculor Pressure Gradient 120 120-
P8760 B76°
Pa
b..87±3 b=87±3
b=94±2 b..94±2
n—B
•
n.=4 n=4
tI10 20 1I
8080 I
10 20 30
0
Fig. 7 Relationships of systemic vascular vascutar pressure pressure gradient gradient (systemic fsystemic arterial mean pressure (SAM) - right atrial mean pressure (RAM)] to thermodilution cardiac output at various barometric pressurs (PB). Symbols
75± 7 b75±7
.
.. • .s .s
100•
0
n6
. •.S S.. . S
(sAM-RAM)
(nviHg)
a=.4±.3
P8 '=282 =282 o-Z2±1 a-Z2±1
I
and other abbreviations as in Fig. 6. (Reprinted with permission from reference 7).
P6 =240 P8=240 a2±1.1 a=2±1.1
o F
0
b74±16 b=74±16
0
'10
20
Cardiac Output (L/min) References
P02 Torr
.
150 140 130 130
.
120 110 100 90
0 o ExerCise Exercise
0
80 10 60 50 40.
30 20 10
0
Cymerman Cymerman A., Reeves J. T., Sutton J. R., Rock P. B., Groves B. M.,
• Rest
pa o°2 A2Pa a2 V2 P02 12 P102
PO P.O2
Malconian M. K., Young P. M., Wagner P. D., Houston C. S.: 22
1987.
MacDougall J. D., Green H. J., Sutton J. R., Coates G., Cymerman
A., Young P., P., Houston Houston C. C.S.: S. Operation Everest Everest II: II: Structural Structural adaptations in skeletal muscle in response to extreme simulated 8
during exercise at altitude, this has very little deleterious effect during on overall gas exchange exchange because because of of the the steepness steepness of of the theoxygen oxygen dissociation curve at altitude. However, the hemodynamic stu-
altitude.ActaPhysiolScand 421—427,1991. altitude. Ada PhysiolScand 142: 142:421—427, 1991. Malconian M., Rock P., Hultgren H. N., Donner H., Cymerman A., Groves B. M., Reeves J. T., Sutton J. R., Nitta M., Houston C.
S.: Operation Everest II: The electrocardiogram during rest and exercise during a simulated ascent of Mt. Everest. A Am mJJ Cardiol 65: 1475— 1480, 1990. 1475—1480,1990.
dies demonstrate marked pulmonary hypertension with increases in pulmonary vascular resistance but myocardial con-
Pugh L. G. C. E.: Resting ventilation and alveolar aic aie on Mount Everest; with remarks barometric pressure to altiremarks on on the the relation relation of ofbarometric
tractility and cardiac output were maintained and there was no ischemia. iscliemia.
Gill, M. B., Milledge J. S., Pugh L. G. C. E., West J. B.: Alveolar gas
composition at 21,000 to 25,000 feet (8,400—7,830 m). J Physiol (Lond) 163:373—377,1962. Green H. J., Sutton J. R., Young P. M., Cymerman A., Houston C. S.: Operation Everest II: Muscle energetics. during maximal exhaustive haustive exercise. JAppiPhysiol 66: 142—150, 142—150, 1989. 1989. Groves B. M., Reeves J. T., Sutton J. R., Wagner P. D., Cymerman A., Malconian M. K., Rock P. B., Young P. M., Houston C. S.: Operation Everest II: Elevated high altitude pulmonary resistance unresponsive to oxygen.JApplPhysiol63: 521 —530, 1987. unresponsivetooxygen.JApplPhysioI63: 521—530,1987. Houston C. S., Riley R. L.: Respiratory and circulatory changes during acclimatization to high altitude. Am JPhysiol 588, during JPhysiol 140: 140: 565— 565—588, 1947. 6 Houston Houston C. S., Sutton J. R., Cymerman A., Reeves J. T.: Operation Everest II: Man at extreme altitude. JAppiPhysiol 63: 877—882,
Fig. 8 Oxygen cascade from inspired air to tissues at various altitudes.
clinical or electrocardiographic evidence of myocardial myocardial
Operation Everest II; Maximal oxygen uptake at extreme altitude. 1989. JApplPhysiol66: 2446—2453,1989. JApplPhysiol66:2446—2453,
10
tude in mountains. JPhysiol(Lond) JPhysiol(Lond) 135: 135:590—160, 590—160, 1957. Reeves J. T., Groves B. M., Sutton J. R., Wagner P. D., Cymerman
A., Malconian M. K., Rock P. B., Young P. M., Houston C. S.:
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160 160 -
J. R. Sutton, T. Reeves, Reeves, B. B. M. M. Groves, P. D. Wagner, Sutton, .1. J. T. Wagner, J.J. K. K. Alexander Alexandereteta!. al.
Operation Everest II: Preservation of cardiac function at great altitude.JApplPhysiol63: 531—539,1987. tude.JApplPhysiol63:531—539, 1987. Rose M. S., Houston C. S., Fulco C. S., Coates G., Sutton J. R., Cy-
merman A.: Operation Everest II: Nutrition and body composi12
13
14
tion.JApplPhysiol6S: 2545—255 1, 1, 1988. 1988. tion.JApplPhysiol65:2545—255 Shi Z. Y., Ningh X. H., Zhu S. C., Zhao D. M., Huang P. G., Yang ascending S. Y., Wang Y., Dong Dong Z. Z. S.: S.:Electrocardiogram Electrocardiogram made on ascending the Mount Qomolangma Qomolangma from from 50 50 m ma. a. s. I. 1. Sc/Sin Sc/Sin 23: 23: 1316—1325, 1316—1325, 1980. Suarez
J. M., Alexander J. K., Houston C. S.: S.; Enhanced left
ventricular systolic performance at high altitude during Operation Everest II. AmJCardioI6O: HAm JCardioI6O: 137—142, 1987. Sutton J. R., Reeves J. T., Wagner P. D., Groves B. M., Cymerman A., Malconian Malconian M. M. K., K., Rock RockP. P.B., B.,Young YoungP.P.M., WalterS. S.D., HousM., Walter D., Houston C. S.: Operation Everest II: Oxygen transport during exercise at extreme simulated simulated altitude. altitude. JAppiPhysiol JAppiPhysiol 64: 64:1309— 1309—1321, 1321, 1988.
15 Wagner P. D., Sutton J. R., Reeves J. T., Cymerman A., Groves B.
M., Malconian M. K.: Operation Everest II: Pulmonary gas exchange during a stimulated ascent of Mt. Everest. J. Appi Physiol 16
63:2348 —2359, 1987. M., Jr. Jr. Pizzo Pizzo C. C. J.: J.: West J. B., Lahiri S., Maret K. G., Peters R. M.,
17
Barometric pressures at extreme altitude on Mount Everest: physiological significance. JAppiPhysiol 54: 1188—1194, 1983. 1983 Zuntz N,, Loewy A., A., Muller Muller F., Caspari W.: Höhenldima N, Loewy Höhenldima und und Bergwanderungen. Berlin: Deutsches Verlagshaus 38: 37—39, 1906.
Dr. J. I R. R. Sutton Sutton Faculty of Health Sciences Sciences The University of Sydney P. 0. Box 170 P.O. Lidcombe NSW, Australia Australia 2141 2141
Increased Arterial Pressure after Acclimatization to 4300 m: Possible Role of Norepinephrine John T Reeves1, Robert S. Mazzeo2 , EugeneE. Wolfe!' andAndrewJ. Young3 1Division of Cardiology, University of Colorado Health Sciences Center, Denver, 80262 2Department of Kinesiology, University of Colorado, Boulder, 80309 3Military Ergonomics Division, United States Army Research Institute of Environmental Medicine, Natick, MA 01760
Abstract John T Reeves, Robert S. Mazzeo, Eugene E. Wolfe! and Andrew I Young, Increased Arterial Pressure
after Acclimatization to 4300 m: Possible Role of Norepinephrine. Tnt J Sports Med, Vol 13, Suppi 1, pp Si 8— S21, 1992.
Both systemic arterial pressure and sympathetic activity increase at high altitude, but neither the time course of these increases nor the relationship between them
are known. Examination of resting and exercising data from our prior studies at sea level and on Pikes Peak indicated that blood epinephrine concentrations either showed little change (from sea level) or rose early in altitude expo-
Int.J.SportsMed. l3(1992)S18—S21 GeorgThieme Verlag StuttgartNew York
sure and then declined with acclimatization. By contrast, norepinephrine concentrations in blood and urine were not increased on arrival but consistently rose later in the acclimatization process. Also with altitude exposure, arterial pressure also increased concomitantly with the increase in norepinephrine concentrations. The study designs were not adequate to establish cause and effect, but the results were consistent with the concept that arterial pressure increments at altitude were associated with increased alpha adrenergic-mediated vascular tone. Key words
Altitude, sympathetic adrenergic activity
activity,
alpha-
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S18 mt.J.J.Sports SportsMed. Med.13 13(1992) S18 mt. (1992)
Oxygen Transport and Cardiovascular Function at Extreme Altitude: Lessons from Operation Operafion Everest II John R. Sutton1, John T ron M. Peter D.Wagner3, Wagner3, James James K. K. Alexander4, Alexander4, T.Reeves2, Reeves2,Bert Bertron M Groves2, PeterD. Cymerman6 and Charles S. Houston7 AllenCyrnerman6 and Charles S. Houston7 Herbert N. Hultgren5 , Allen 'Department of Biological Sciences, Faculty of Health Sciences, The University of Sydney 2Department of Medicine, University of Colorado, Denver, CO, U. S. A. 3Department of Medicine, University of California, San Diego, La Jolla, CA, U. S. A. 92093 4Department of Internal Medicine, Baylor College of Medicine, Houston, TX, U. S. A. 77030 5Department of Cardiology, Veterans' Administration Medical Centre, Palo Alto, CA, U. S. A. 94304 6Altitude Research Division, U. S. Army Research Institute of Environmental Medicine, Natick, MA, U. S. A. 01760-5007 7Department of Medicine, Vermont, Burlington, VT, U. S. A. Medicine, University University of ofVermont, A. 04501 04501
Abstract John R. Sutton, John T. Reeves, Bertron M. Groves, Peter D. Wagner, James K. Alexander, Herbert N. Hultgren, Allen Cymerman and Charles S. Houston, Oxygen
Transport and Cardiovascular Function at Extreme Altitude: Lessons from Operation Everest II. Tnt J Sports Med, Vol 13,Suppl 1,ppSl3—518, 1,ppSl3—Sl8, 1992.
Operation Everest II was designed to examine the physiological responses to gradual decompression simulating an ascent of Mt Everest (8,848 m) to an inspired P02 of 43 mmHg. The principal studies conducted were cardiovascular, respiratory, muscular-skeletal and metabolic responses to exercise. Eight healthy males aged
21—31 years began the "ascent" and six successfully reached the "summit", where their resting arterial blood mmHg and andPCO2 PCO2 11 11mmHg, mmHg, pH pH gasses were P02 = 30 mmHg = 7.56. Their maximal oxygen uptake decreased from L/minatatsea sealevel level to to 1.17 1.17 0.08 0.08 L/min at P102 3.98 0.2 L/min 3.98 43 mmHg. The principal factors responsible for oxygen transport from the atmosphere to tissues were (1) Alveolar ventilation — a four fold increase. (2) Diffusion from the alveolus to end capillary blood — unchanged. (3) Cardiac function (assessed by hemodynamics, echocardiography normal — although although maximum and electrocardiography) — normal cardiac output and heart rate were reduced. (4) Oxygen extraction — maximal with Pv02 14.8 1 mmHg. With in-
creasing altitude maximal blood and muscle lactate progressively declined although at any submaximal intensity blood and muscle lactate was higher at higher altitudes. Key_words
Altitude, exercise, cardiac output, hypobaric chamber, chamber, pulmonary pulmonary circulation circulation
mt. J.J.Sports Tnt. SportsMed. Med.13(1992)S13 l3(l992)S13 — S18
GeorgThieme Georg ThiemeVerlag VerlagStuttgart StuttgartNew New York
In the world of mountain medicine, there are four dates in this century of particular significance. At these times, important knowledge was gained about adaptations to extreme altitude on Mount Everest. On the first, May 29, 1953, Edmund Hillary and Tenzing Norgay reached the summit. Electrocardiograms of four climbers were telemetered from the summit in May of 1975 during the Chinese Mount Qomolangma expedition (12). On May 8, 1978, Peter Habeler and Reinhold Messner completed the first ascent of of Mount Mount Everest Everest without the use of supplementary oxygen. oxygen. On On October October
24, 1981, Chris Pizzo made the first measurements of barometric pressure and other physiological variables on the summit (16). On each occasion, significant new knowledge was was gained gained which which helped helped our our understanding understanding of of altitude altitude physiphysiology. The first piece of information was that the summit of Mount Everest could be reached by humans. The second was that some measurements could be made. The third was that it was not necessary to use supplementary oxygen to accomplish the climb. However, as was clear from the American Medical Research Expedition to Everest which made some simple, non-invasive measurements, and from experience in other mountain locations, detailed physiological measurements at extreme altitudes, particularly those involving invasive techniques, were highly risky, if not impossible, at our present state of knowledge and technology.
Two other dates are important in the world of mountain medicine. They are July 30, 1946 and November 8, 1985. On the first date, two subjects reached a barometric pressure of 235 Torr in a small hypobaric chamber during the historic Operation Everest study conducted by Charles Houston and Dick Riley (5). In the second instance, six subjects were taken to a barometric pressure pressure of of 234 234 Torr Torr during during the the study study
Operation Everest II under the the investigative investigative guidance guidance of of Charles Houston, Allen Cymerman and John Sutton (6). Although both Operation Everest and its successor, Operation Everest II (OEII), were prolonged hypobaric chamber studies and nearly 40 years elapsed between the studies, perhaps the most remarkable fact was that Charles Houston was a principal investigator of both projects.
The principal objectives of OEII were to examine all the physiological variables which determine oxygen
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Introduction
514 mt. S14 mt. .1. i Sports SportsMed. Med.13(1992) 13(1992)
I R. J. R.Sutton, Sutton,IITTReeves, Reeves, B. B. M M Groves, Groves, P. P. B. B. Wagner, Wagner, I K. Alexander etal.
transport, from the lung and alveolar ventilation to oxygen extraction at the tissue level, and muscle structure and function (4,6, (4, 6,10, 10, 14, 14, 15). 15). In In order order to to do do this, this, a variety of exercise studies were performed including the measurement of maximal oxy(VO2max)(l). gen uptake (VO2max) (1).Invasive Invasivestudies studieswere weremade madein inwhich which
an arterial line and a Swan-Ganz catheter were inserted to measure pulmonary hemodynamics, arterial blood gases and cardiac output directly using the Fick technique. In addition, a
ASCENT PROFILE F 02 F 02 Torr Torr 43 49
63 80
superficial venous line was inserted for the infusion of inert gases to quantify ventilation/perfusion relationships (15). In a third study, venous blood and muscle biopsy samples were taken after exercise to exhaustion (3, 14). Two additional exercise studies were performed to gain further information on car-
/ 150
L5
10 15
20 25 30 35 40
DAYS AT ALTITUDE
diac function. One was two-dimensional echocardiography (13) and the other was 12-lead electrocardiograms (8). Fig.
1 Ascent profile of Operation Everst II.
ergometer, a treadmill, a table, a water fountain and chairs.
ter Calibration Curve is lower than either of these, projecting a figure of approximately 235 Torr for the summit. This figure has has been been used used traditionally traditionally in in all all decompression decompression chamber chamber stustudies since, including Houston and Riley's original Operation Everest project. However, when measurements were made at extreme altitudes in the Himalaya by Pugh in 1957 (9) and Gill and coworkers in 1962 (2), the derived figure for the summit of Mt. Everest was 250 Torr. In 1981, on the AMREE trip, Pizzo
The smaller room was the principal study site. In the lock were
recorded a measurement of 253 Torr, confirming the earlier
placed a toilet and shower and the "Versaclimber" used to
work of Pugh and colleagues (9).
The decompression chamber consisted of two rooms, 6.1 x 2.7 m and 2.7 2.7 xx 3.7 3.7 m m in in size, size, connected connected by byan an airlock of 2.7 x 2.1 m which could be decompressed independently of the rooms. In each chamber, there was a small pass-through lock to enable the shipping out of samples and the shipping in of food. The larger room served as the living
quarters and contained four double bunk beds, a cycle
enable the subjects to simulate climbing.
Operation Everest II Subjects The The subjects were all men, ranging in age from 21 to 31 years, of varying backgrounds from bicycle mechanic and draftsman to medical students and physicians.
After extensive studies at sea level, the chamber ber doors were closed and for 40 days and nights, nights, the the subjects subjects were were gradually gradually decompressed decompressed (Fig. (Fig. 1). 1). On On three three occasions, occasions, at at barometric pressures of 429, 380 and 347 Torr, the chamber was kept constant for several days to enable the scientists to perform more detailed and invasive studies of all the subjects at one pressure. When the chamber was decompressed to 308 Torr, the equivalent of 7,010 m, the subjects had difficulty sleeping, so the chamber pressure was reduced each night by 4—6 Torr to effectively accomplish what mountain climbers do — climb high and sleep low. Finally, on day 34, November 8,
1985, we had our first "summit run", taking the subject from 282 Torr to a final barometric pressure of 234 Torr, over 9,000 m, without any ill effects. This demonstrated to the subjects that they were capable of reaching this simulated altitude and was very important psychologically since they knew that the next time they were to reach the summit, they would be required to perform a maximal exercise test with indwelling arterial and central venous lines. Over the course of the next week, the subjects were studied at 282 Torr and gradually decompressed to the equivalent of the summit of Everest.
Paul Bert suggested that the barometric pressure on the summit of Mt. Everest would be approximately 250 Torr. Earlier in this century, Zuntz and colleagues made measurements as high as 4,980 m and predicted a much higher pressure for that summit — 269 Torr (17). The International Altime-
In the autumn of 1985, a group of 26 scientists and 8 subjects embarked on the Operation Everest II project.
The main purpose was to examine in detail components of oxygen transport during exercise at extreme simulated altitude. Although detailed measurements were made of psychology, body composition, nutritional status, muscle biochemistry, structure and function, endocrine function and control of breathing at rest and during sleep, in this paper we shall detail the features of oxygen transport and emphasize cardiac function.
Several exercise studies were were performed performed in in order to quantify oxygen transport and cardiovascular function. They include: I. An 1. An interrupted interrupted VO2max test to quantify maximal oxygen uptake — also also at extreme altitude 12-lead electrocardiographs were taken looking for morphological changes related to pulmonary hypertension and also seeking evidence of of myocardial ischemia. 2. 2. A progressive exercise test to exhaustion, with with the the workload workload beginning at 30 W and increasing in 30 W increments each minute. This test was used to quantify maximum power output, maximum heart rate, exercise symptoms of leg fatigue and dyspnea, and maximal blood lactate. At rest and exhaustion in this test, muscle biopsy samples were taken from the vastus lateralis for analysis of enzymes, muscle metabolites and muscle ultrastructure. 3. Two-dimensional echocardiograms with pulsed Doppler recordings were performed at rest and during exercise at various altitudes from sea level up to and including the equivalent of the summit of Mt. Everest.
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The Chamber
Jnt.J.J. Sports mt. Sports Med. Med. 13 13(1992) (1992) S15
Oxygen Transport and Cardiovascular Function at Extreme Altitude
4. Several levels of steady-state exercise up to and in some cases including maximal oxygen uptake with indwelling brachial or radial arterial lines and a Swan-Ganz flowdirected thermodilution catheter inserted into the pulmonary artery. In addition, a superficial venous catheter was
weighing and computerized axial tomography scans con-
inserted to enable us to infuse various inert gases to quantify
sea level level value, value,from fromaamean meanofof5050ml-kg-min mlkgmin'at the sea 'at sea sea level kg level to to15 15mlml-kgmin' on"thesummit"(Fig.2). on "the summit" (Fig. 2).
ventilation/perfusion relationships. This study included
firmed that both fat and lean muscle tissue were lost during the course of this decompression (11).
Maximal oxygen uptake decreased by 72% of
the most invasive procedures and gave us the opportunity to
of the direct Fick technique to quantify cardiac output. Findings and Implications of Operation Everest II
Of the eight subjects who began the study, two were removed from the chamber prematurely for hypoxic episodes, but six were able to reach the "summit" and exercise. Over the course of 40 days and nights, there was a mean weight loss of 7.44 kg (8.9%) as the subjects had a marked reduction (42%) in caloric intake despite being provided with excellent
and appetizing meals. Skinfold measurements, underwater
60 MeanSEM
50 C
There were progressive changes changes in in the the resting resting electrocardiograms: an increase increase in in P-wave P-wave amplitude, amplitude, aaright right axis shift in the frontal plane — compatible compatible with pulmonary hypertension with increasing altitude. No arrythmias, conduction defects, ST- or T-wave changes to suggest ischemia were observed despite profound hypoxemia (8). In the progressive exercise test to exhaustion, with increasing altitude, exercise performance was decreased,
accompanied by a diminished maximum heart rate and increased ventilation. At extreme extreme altitude, altitude, the the overwhelming overwhelming symptoms of dyspnea and leg fatigue were of a comparable order of magnitude, each reaching 9.5 on the Borg 0—10 scale.
In this study, blood lactate was also analyzed and at exhaustion, showed a progressive decrease from 12.7 mmol-F 1at theequivalent equivalent of of the summit of of sea level level to to 3.4 3.4mmol-F mmolF 1atatthe Mt. Everest (14). The muscle biopsy samples taken at exhaustion showed a progressive decrease in muscle lactate at exhaustion with increasing altitude (3).
In the echocardiographic study, all subjects 40 40
had a decreased left ventricular end-diastolic and end-systolic
30
volume and stroke volume decreased progressively. progressively. These These changes were of these orders of magnitude: 21%, 40% and
a,
14% respectively at a barometric pressure of 282 Torr (Fig. 3). There were comparable decreases during exercise at 60 W intensity. 1n addition, indices of left ventricular systolic function — ejection fraction, the ratio of peak systolic pressure to endsystolic volume, and the mean normalized systolic ejection rate — were were either maintained or slightly enhanced at altitude, suggesting a modest increase in left ventricular contractility at altitude (13; Fig. 4). During maximal exercise, no ST-T wave
•: 0-
______________
I—I I
434963
I 150
I
80
changes were seen in the electrocardiogram to suggest
P102 Torr
ischemia or left ventricular dysfunction and no significant arrhythmias occurred.
Fig. Fig. 2 VO2max 'O2max with with altitude. altitude.
Fig. Ejection fractions fractions at at rest rest on on the the Fig. 33Ejection
an —
80
80
70
70
60
60
50
50
EjectIon Ejection Fraction FracUon
(°/)
cycle ergometer and during peak exercise in all sublects subjects studied at sea level and at a barometric pressure of 282 Torr. (Reprinted with permission from reference 12.)
Mean
Mean
40L Cycle
Peak
Cycle
Rest
Exercise
Rest
Sea Levet Level
Peak Exercise
8 282 torr
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measure arterial and mixed venous blood gases and systemic and pulmonary hemodynamics, together with the use
I R.R.Sutton, .1. Sutton, II T Reeves, Reeves, B.B.MMGroves, Groves, P. D. P. Wagner, D. Wagner, J. K. J. Alexander K. Alexander ci al. el al.
S16 mt. I Sports Med. 13(1992) 12
Ô L/min
P 282 torr 10 O—O P9 380 torr
b— Sea Level Ratio Peak Systolic Pressure: End-Systolic Volume Vol urn e (rnrn Hg/rnI) (mm Hg/mi)
24 20
8 6
.150 £80
16 12
4
2 I
CI C
Peak Exercise
Cycle Rest
(Torr) •63 V 49 .43
8 4 0
POWER OUTPUT WATTS
Fig. 4 Mean ratios of peak systolic pressure to end-systolic volume volume at at rest rest on on the the cycle cycle ergometer ergometer and and during during peak peak exercise exercise for for a!! subjects studied at sea eveJ, all level, and barometric barometric pressures pressures of of 380 380 Torr and 282 Torr. (Reprinted with permission from reference 12).
60 120 180 240 300 360
Fig. 5 Cardiac output during exercise with increasing simulated
There There were substantial changes in the right side of the heart. As noted earlier, there was a rightward of rightward deviation deviation of the mean QRS axis in the frontal plane on the electrocardiogram; this was presumably a concomitant of the pulmonary hypertension. There was also a moderate right ventricular enlargement and paradoxial septal wall motion seen on the echocardiogram (13). Right ventricular filling pressures (denoted by right atrial mean pressure) did not increase with altitude, nor did the Doppler examination reveal evidence of tricuspid valve valve incompetence. incompetence. Left Left ventricular ventricular filling tilling pressure also remained normal or decreased with increasing altitude altitude expoexposure, as reflected by pulmonary artery wedge pressure. This may be related, in part, to a decrease in plasma volume. We concluded from the echocardiographic studies that ventricular function remained normal, was even enhanced and was not a limiting factor in exercise performance at extreme altitude.
The most comprehensive exercise studies performed in OEII enabled us to quantify all aspects of oxygen transportation as we had indwelling arterial and pulmonary artery catheters. Our principal observations indicated that the major adjustments in the oxygen transport system which allowed exercise to be performed at extreme altitude were adaptations in ventilation, an increase in hemoglobin and in maximizing oxygen extraction (14). The chief value of arterial and mixed venous blood gases at VO2max are seen in Table 1. On
"the summit", P02 fell to 27.6 Torr at 120 W exercise. The lowest individual oxygen tension was 26 Torr, with with aa mean mean oxygen uptake of 1.18 l-min1. 1min1. The inert gas studies of of WagWagner ner and colleagues (15) showed that with increasing increasing altitudes altitudes below 429 Torr, the widening of the alveolar to arterial oxygen tension difference ((A — a)D02) became increasingly due to to aa
diffusion limitation and less due to the ventilation-perfusion mismatch.
Cardiovascular physiology in this study revealed vealed that that cardiac cardiac output output for for aa given given oxygen oxygen uptake uptake was was simisimi-
lar at all altitudes, although perhaps slightly higher on "the summit" (Fig. 5); however, the potential advantage of increas-
ing cardiac output to offset the marked arterial desaturation and decreased arterial oxygen content was not used. Resting pulmonary artery pressure and pulmonary vascular resistance increased from sea level to to maximum maximum values values at at PB PB 282 282 Torr Torr from 15 to to 34 34 mmHg mmHgand andfrom from1.2 1.2toto4.3 4.3mmHg-l-min1remmHglmin1respectively (Fig. 6). The increase was magnified during exercise, where the pulmonary artery pressure at sea level was 33 mmHg, rising to 54 mmHg at 282 Torr. Right atrial and pulmo-
nary artery wedge pressures did not increase at altitude, nor did systemic arterial pressure or systemic vascular resistance (Fig. 7). Conclusion
Table 1
VO2max, arteria' arterial (Pa02) (Pa02) and and mixed mixed venous venous(PV02) (PO2) oxygen oxygen tension at maximum exercise at different simulated altitudes. At the highest simulated altitude, a pressure of 240 Torr was required to give a Pi02 of 43 Torr as the inspired oxygen concentration had increased to 22% due to the excess oxygen exhaled by the scientists who were breathing 100% oxygen while working in the chamber. This is further detailed in reference 5. PB Pa (Torr)
P102 Pi02
n
760 429 347
150
282 240
49
80 63 63 43
8 8
7 5 5
Pa02
VO2max
(mImin (mImin
(Torr)
1)
(Torr)
PV02 PO2 (Torr)
3980 3,980 2,820 2060 2,060
87.3 87.3 41.9
18.5 ———
33.7
12.4
1770 1,770
33.1
14.1
1170 1,170
27.6
13.8
The Operation Everest II studies gave us some insight into how it is possible to climb to the equivalent of the summit of Mt. Everest without the use of supplementary oxygen. Performing exercise which can require more than one liter of oxygen but in which arterial oxygen tension is less than 30 Torr, the major mechanisms which come into play are: 1. a four-fold increase in ventilation 2. a 33% increase in hemoglobin 3. maximal oxygen extraction (Fig. 8)
Ventilation-perfusion studies indicated that gas transfer in the lung is primarily diffusion-limited. While ventilation/perfusion inequality inequality is is considerably considerably increased increased
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altitude.
:
mt. J. Sports Med.13 13(1992) Int.J.SportsMed. (1992) S17
Oxygen Transport and Cardiovascular Function at Extreme Altitude 50 50-Pulmonary 40 Vos culor Vascular Pressure 30 30 Gradient (PAM—PAWU)
20 -
(mml-4g) (mmkg)
0
C
a
• 0-
n—6
5/ .,
-
I
j
p/
•,L7' //P8 P6=240 =240
I
I
10 20 io 20
o 0
Fig. 6 Relationships of mean pulmonary
, •IS
/ ' a—2.77±.65 '0 b——1±bO b— —1±10 '0 n3
i:. •
I- 1I20 30
10
'
n—2
S7 / IS "S
b—12±2 b—12±2
a—24±.07 a—.24±.07
10 --
b—lU b-b
12 a— 1. 09± .12 01,09±.
P8 = 760 760 b—6±1 n—B n—B
B282 a—2.36 o—2.36 P8 = 282
P =347 PB=347
0
20
10
vascular pressure gradient [pulmonary arterial mean pressure (PAM) — pulmonary arterial wedge mean pressure (PAWM)] to thermodilution modilution cardiac output at various barometric pressurs (PB). Measurements are shown for PB 760, 347, 282 Torr (filled
circles) and 240 Torr (open circles). A regression line, y = ax + b , was calculated ca)culated for each subject at at each each PB. Pa. Shown, averaveraged for each PB, are slopes &opes (a) and intercepts (b) of regression equations, number of subjects (n), and regression line for group. (Reprinted with permission from reference 7).
Cardiac Output CL/mm)
Systemic
140 Vascular 140Vosculor Pressure Gradient 120 120-
P8760 B76°
Pa
b..87±3 b=87±3
b=94±2 b..94±2
n—B
•
n.=4 n=4
tI10 20 1I
8080 I
10 20 30
0
Fig. 7 Relationships of systemic vascular vascutar pressure pressure gradient gradient (systemic fsystemic arterial mean pressure (SAM) - right atrial mean pressure (RAM)] to thermodilution cardiac output at various barometric pressurs (PB). Symbols
75± 7 b75±7
.
.. • .s .s
100•
0
n6
. •.S S.. . S
(sAM-RAM)
(nviHg)
a=.4±.3
P8 '=282 =282 o-Z2±1 a-Z2±1
I
and other abbreviations as in Fig. 6. (Reprinted with permission from reference 7).
P6 =240 P8=240 a2±1.1 a=2±1.1
o F
0
b74±16 b=74±16
0
'10
20
Cardiac Output (L/min) References
P02 Torr
.
150 140 130 130
.
120 110 100 90
0 o ExerCise Exercise
0
80 10 60 50 40.
30 20 10
0
Cymerman Cymerman A., Reeves J. T., Sutton J. R., Rock P. B., Groves B. M.,
• Rest
pa o°2 A2Pa a2 V2 P02 12 P102
PO P.O2
Malconian M. K., Young P. M., Wagner P. D., Houston C. S.: 22
1987.
MacDougall J. D., Green H. J., Sutton J. R., Coates G., Cymerman
A., Young P., P., Houston Houston C. C.S.: S. Operation Everest Everest II: II: Structural Structural adaptations in skeletal muscle in response to extreme simulated 8
during exercise at altitude, this has very little deleterious effect during on overall gas exchange exchange because because of of the the steepness steepness of of the theoxygen oxygen dissociation curve at altitude. However, the hemodynamic stu-
altitude.ActaPhysiolScand 421—427,1991. altitude. Ada PhysiolScand 142: 142:421—427, 1991. Malconian M., Rock P., Hultgren H. N., Donner H., Cymerman A., Groves B. M., Reeves J. T., Sutton J. R., Nitta M., Houston C.
S.: Operation Everest II: The electrocardiogram during rest and exercise during a simulated ascent of Mt. Everest. A Am mJJ Cardiol 65: 1475— 1480, 1990. 1475—1480,1990.
dies demonstrate marked pulmonary hypertension with increases in pulmonary vascular resistance but myocardial con-
Pugh L. G. C. E.: Resting ventilation and alveolar aic aie on Mount Everest; with remarks barometric pressure to altiremarks on on the the relation relation of ofbarometric
tractility and cardiac output were maintained and there was no ischemia. iscliemia.
Gill, M. B., Milledge J. S., Pugh L. G. C. E., West J. B.: Alveolar gas
composition at 21,000 to 25,000 feet (8,400—7,830 m). J Physiol (Lond) 163:373—377,1962. Green H. J., Sutton J. R., Young P. M., Cymerman A., Houston C. S.: Operation Everest II: Muscle energetics. during maximal exhaustive haustive exercise. JAppiPhysiol 66: 142—150, 142—150, 1989. 1989. Groves B. M., Reeves J. T., Sutton J. R., Wagner P. D., Cymerman A., Malconian M. K., Rock P. B., Young P. M., Houston C. S.: Operation Everest II: Elevated high altitude pulmonary resistance unresponsive to oxygen.JApplPhysiol63: 521 —530, 1987. unresponsivetooxygen.JApplPhysioI63: 521—530,1987. Houston C. S., Riley R. L.: Respiratory and circulatory changes during acclimatization to high altitude. Am JPhysiol 588, during JPhysiol 140: 140: 565— 565—588, 1947. 6 Houston Houston C. S., Sutton J. R., Cymerman A., Reeves J. T.: Operation Everest II: Man at extreme altitude. JAppiPhysiol 63: 877—882,
Fig. 8 Oxygen cascade from inspired air to tissues at various altitudes.
clinical or electrocardiographic evidence of myocardial myocardial
Operation Everest II; Maximal oxygen uptake at extreme altitude. 1989. JApplPhysiol66: 2446—2453,1989. JApplPhysiol66:2446—2453,
10
tude in mountains. JPhysiol(Lond) JPhysiol(Lond) 135: 135:590—160, 590—160, 1957. Reeves J. T., Groves B. M., Sutton J. R., Wagner P. D., Cymerman
A., Malconian M. K., Rock P. B., Young P. M., Houston C. S.:
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160 160 -
J. R. Sutton, T. Reeves, Reeves, B. B. M. M. Groves, P. D. Wagner, Sutton, .1. J. T. Wagner, J.J. K. K. Alexander Alexandereteta!. al.
Operation Everest II: Preservation of cardiac function at great altitude.JApplPhysiol63: 531—539,1987. tude.JApplPhysiol63:531—539, 1987. Rose M. S., Houston C. S., Fulco C. S., Coates G., Sutton J. R., Cy-
merman A.: Operation Everest II: Nutrition and body composi12
13
14
tion.JApplPhysiol6S: 2545—255 1, 1, 1988. 1988. tion.JApplPhysiol65:2545—255 Shi Z. Y., Ningh X. H., Zhu S. C., Zhao D. M., Huang P. G., Yang ascending S. Y., Wang Y., Dong Dong Z. Z. S.: S.:Electrocardiogram Electrocardiogram made on ascending the Mount Qomolangma Qomolangma from from 50 50 m ma. a. s. I. 1. Sc/Sin Sc/Sin 23: 23: 1316—1325, 1316—1325, 1980. Suarez
J. M., Alexander J. K., Houston C. S.: S.; Enhanced left
ventricular systolic performance at high altitude during Operation Everest II. AmJCardioI6O: HAm JCardioI6O: 137—142, 1987. Sutton J. R., Reeves J. T., Wagner P. D., Groves B. M., Cymerman A., Malconian Malconian M. M. K., K., Rock RockP. P.B., B.,Young YoungP.P.M., WalterS. S.D., HousM., Walter D., Houston C. S.: Operation Everest II: Oxygen transport during exercise at extreme simulated simulated altitude. altitude. JAppiPhysiol JAppiPhysiol 64: 64:1309— 1309—1321, 1321, 1988.
15 Wagner P. D., Sutton J. R., Reeves J. T., Cymerman A., Groves B.
M., Malconian M. K.: Operation Everest II: Pulmonary gas exchange during a stimulated ascent of Mt. Everest. J. Appi Physiol 16
63:2348 —2359, 1987. M., Jr. Jr. Pizzo Pizzo C. C. J.: J.: West J. B., Lahiri S., Maret K. G., Peters R. M.,
17
Barometric pressures at extreme altitude on Mount Everest: physiological significance. JAppiPhysiol 54: 1188—1194, 1983. 1983 Zuntz N,, Loewy A., A., Muller Muller F., Caspari W.: Höhenldima N, Loewy Höhenldima und und Bergwanderungen. Berlin: Deutsches Verlagshaus 38: 37—39, 1906.
Dr. J. I R. R. Sutton Sutton Faculty of Health Sciences Sciences The University of Sydney P. 0. Box 170 P.O. Lidcombe NSW, Australia Australia 2141 2141
Increased Arterial Pressure after Acclimatization to 4300 m: Possible Role of Norepinephrine John T Reeves1, Robert S. Mazzeo2 , EugeneE. Wolfe!' andAndrewJ. Young3 1Division of Cardiology, University of Colorado Health Sciences Center, Denver, 80262 2Department of Kinesiology, University of Colorado, Boulder, 80309 3Military Ergonomics Division, United States Army Research Institute of Environmental Medicine, Natick, MA 01760
Abstract John T Reeves, Robert S. Mazzeo, Eugene E. Wolfe! and Andrew I Young, Increased Arterial Pressure
after Acclimatization to 4300 m: Possible Role of Norepinephrine. Tnt J Sports Med, Vol 13, Suppi 1, pp Si 8— S21, 1992.
Both systemic arterial pressure and sympathetic activity increase at high altitude, but neither the time course of these increases nor the relationship between them
are known. Examination of resting and exercising data from our prior studies at sea level and on Pikes Peak indicated that blood epinephrine concentrations either showed little change (from sea level) or rose early in altitude expo-
Int.J.SportsMed. l3(1992)S18—S21 GeorgThieme Verlag StuttgartNew York
sure and then declined with acclimatization. By contrast, norepinephrine concentrations in blood and urine were not increased on arrival but consistently rose later in the acclimatization process. Also with altitude exposure, arterial pressure also increased concomitantly with the increase in norepinephrine concentrations. The study designs were not adequate to establish cause and effect, but the results were consistent with the concept that arterial pressure increments at altitude were associated with increased alpha adrenergic-mediated vascular tone. Key words
Altitude, sympathetic adrenergic activity
activity,
alpha-
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S18 mt.J.J.Sports SportsMed. Med.13 13(1992) S18 mt. (1992)
